Letter to the Editor

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Cell, Vol. 88, 9–11, January 10, 1997, Copyright 1997 by Cell Press

Letter to the Editor

Secreted Fringe-like Signaling Molecules May Be Glycosyltransferases Pattern formation during development requires the regulated expression of numerous signaling molecules. One of these, Drosophila Fringe (FNG) is a novel secreted protein with a key role in dorsal-ventral aspects of wing formation (Irvine and Wieschaus, 1994). Recently, multiple functions have been assumed for a Xenopus homologue (lunatic Fringe, lFNG) including the induction of mesoderm; a complex expression pattern supports this notion (Wu et al., 1996). Complex and general functions of Fringe-like proteins are also indicated by the presence of two divergent C. elegans and at least six human homologues identifiable by sequence database searches (Figure caption). Thus, conservation patterns within the FNG family emerge that allow the use of sensitive motif and profile searches (for details see Bork and Gibson, 1996). Indeed, we found significant similarities of FNG-like proteins to Drosophila Brainiac (BRN; Goode et al., 1996) and, surprisingly, also to the Lex1 family of biosynthetic galactosyltransferases (Figure 1). BRN has been proposed to be required for proper contact or adhesion between germline and follicle cells (Goode et al., 1992,1996). BRN and FNG share several features: i) they are developmentally regulated, secreted signaling molecules without known receptors, ii) they are required during (dorso-ventral) epithelial patterning (Irvine and Wieschaus, 1994; Wu et al., 1996; Goode et al., 1996), iii) they interact genetically with the Notch and/or EGF receptor pathways (Kim et al., 1995; Goode et al., 1996), suggesting that they might modify the signaling mediated by these receptors, and iv) FNG and BRN both have at least two C. elegans and several human homologues suggesting the presence of multigene families (Figure 1). Lex1 of Haemophilus influenzae is essential for the biosynthesis of its extracellular lipooligosaccharides (LOS) (Cope et al., 1991) as is its homologue in another parasitic bacterium, Pasteurella haemolytica (Potter and Lo, 1995). In two other parasites with a similar LOS architecture, Neisseria meningitidis and Neisseria ghonorrhoeae, two highly related proteins of the Lex1 family have been independently characterized in each organism as galactosyltransferases (Gotschlich, 1994; Jennings et al., 1995) that add galactose to glucose or N-acetylglucosamine residues of the LOS (Jennings et al., 1995). The LOS of all these parasitic bacteria contain epitopes that are antigenically and structurally very similar to carbohydrates present in human glycosphingolipids; the parasites are thus able to mimic the latter (Mandrell et al., 1992). Furthermore, the bacterial galactosyltransferases are significantly similar (blast (Altschul

et al., 1994) value for the probability of matching by chance p 5 1.9x1027) to a putative secreted protein from C. elegans (Figure 1) as well as to human and mouse ESTs (blast p-values